The purpose of the pilot project component of this U19 application is to provide a resource for funding new research opportunities that are considered high risk yet with a high potential for making new in-roads into the study of human immunology in the context of agents categorized as A-C by NIAID, NIH. The scientific merit of these applications will be judged primarily as the potential of the projects to produce data with the highest likelihood to result in RO1 funding. With these objectives in mind, we have selected a group of senior scientists who have a record of judging grant applications, shown by their history of serving on NIH study sections, their ability to obtain NIH funding and their stature in the Immunology community to serve on the administrative committee in charge of selection of the pilot grants. Each of the individuals who have agreed to serve are established authorities in the field of Immunology with solid administration experience and national recognition. They include Drs. Ansari, Jensen, Rich and Stephens. In addition, we are very fortunate to have the preeminent national bio-defense laboratories of the CDC located within close proximity of Emory University, School of Medicine. More importantly, several of us, including the P.I. of this U19 application, Dr. Rafi Ahmed, and Drs. Jensen, Ansari and Stephens have close working relationships with several of the components of the CDC, including the Special Pathogens Branch. The working relationships are exemplified by joint publications with CDC investigators. With the focus on biodefense for this RFA, we thus have selected 2 investigators (Drs. Damon/poxvirus work and Dr. Quinn/anthrax work) from the CDC to join us in the administration of this pilot project component. They will each contribute immensely from their individual levels of knowledge and expertise on issues related to biodefense to insure that the pilot projects chosen for funding have this relevant component appropriately included and addressed in the selected research proposals. The proposal outlines the pilot projects administrative committee members, the scope of the pilot projects, eligibility and funding guidelines to be utilized, methods we will utilize to seek applications for the pilot projects, the selection criteria we will utilize for funding the projects, milestones that we will use to monitor progress of the pilot projects, an outline for insuring quality of the pilot projects and finally, incentives that we believe are important to provide to individuals who are successful in obtaining RO1 funding. Finally, as required, examples of 2 pilot projects that we would consider for funding under this component of the U19 application are provided. These include studies of the molecular basis for human regulatory T-cell function (Dr. F. Sallusto) and mechanisms by which small pox virus influences immune responses (Dr. Silvestri).